Current Proprietary Norms (Briefing Note)

SUMMARY

This brief summarizes a selection of intellectual property (IP) and data and materials sharing statements from major funders of hESC research in the US and UK.  Significant areas of broad agreement exist regarding the need to consider social benefit in IP policy; the usefulness for scientific progress of early dissemination and publication of data or results; and the need for materials sharing agreements for scientific integrity.  However, significant uncertainty exists regarding how to operationalize these general norms, whether by defining more clearly social benefits or how these are balanced; considering alternatives to IP; creating accountability mechanisms; defining incentives for sharing; and improving coordination in hESC research.

BACKGROUND

Identifying the challenges raised internationally by current proprietary structures in stem cell research requires ongoing examination of stated norms and actual practices.  While the situation in hESC research is not unique, general concerns about deterioration of scientific openness and the norm of sharing expressed over the past several decades come into clearer focus in hESC research; this results in part from the unique technical, policy/regulatory, and ethical context of hESCs.  First, a limited number of cell lines and the high level of technical expertise required to manipulate them make hESC research technically inaccessible to many scientists.  Second, special policies and regulatory frameworks exist regarding hESCs (e.g., the federal funding limitations experienced in the US).  Third, hESCs have attracted special ethical attention, as a result of the destruction of human embryos necessary for their derivation; this had implications, for example, when the European Patent Office rejected a hESC patent as contrary to “public order.”

Nonetheless, hESC research continues to advance, and the first US clinical trial of a hESC-based intervention began in October 2010. In order address the proprietary challenges raised by IP and data/materials sharing practices in stem cell research, one must identify norms as they currently exist and are reflected in major policies and guidance related to hESC research. Doing so reveals significant areas of agreement, as well as areas of uncertainty.

AREAS OF BROAD AGREEMENT

(1) Intellectual Property and “Social Benefit.” In all but a few examples, stated IP policy encourages patents only when necessary for commercialization; the use of non-exclusive licenses as a default option; and the consideration of “social benefits” in determining IP practices.

For example, the US NIH encourages patenting when “necessary;” the NIH policy may be seen as a norm setter for state-based organizations whose own policies are similar to the NIH (e.g., CIRM).  In the UK, the MRC considers “wider social benefits” in its IP practices, as does the Wellcome Trust.  Patents are typically owned by the individual or institution performing the work, rather than the funder (notable exceptions include the Australian Stem Cell Centre and Stem Cells 4 Safer Medicines). Most policies that address licensing specifically suggest use of non-exclusive licensing wherever possible, and some (e.g., CIRM) request the grantee to set benchmarks or milestones for licensees.  When concern exists about IP policy and practices, some major funders (US NIH, UK Wellcome Trust, CIRM) retain march-in rights, which allows an institution, such as the NIH, to require licensing or to grant a license itself.

(2)  Data and Materials Sharing. More so than in patenting and licensing, stated policies on data and materials sharing emphasize – both from a social benefits perspective and from within the norms of science – that data and materials should be shared as widely as possible and without undue restriction.

For example, the UK MRC allows few exceptions for data sharing, except as needed to protect privacy/confidentiality, national security, a time-delimited right of data creators for their own work, or for intellectual property reasons as above.  The US NIH requires a data sharing plan for grants over US$500,000.  The justification for sharing in these contexts is, in part, their publicly funded nature.  Journals (e.g., Nature, Science) are critical to the dissemination of hESC research findings and require data and material sharing without “undue qualification” both before and after the peer review process in order to  meet scientific norms of reproducibility and integrity.  Most journals also participate in free access initiatives to publicly funded research (e.g., PubMed Central).  A few institutions, such as California’s CIRM, attach specific timeframes (60 days) to respond to requests for data and materials sharing.

(3) The Need for Registries and Stem Cell Banks. Increasingly, researchers and others have recognized a need for international registries of hESCs (i.e., databases of technical materials related to individual cell lines) and international stem cell banks (i.e., repositories from which researchers can obtain cells).  These initiatives should provide a means by which data and materials can be more easily shared; at present they do not address specifically IP policies or the terms of licensing arrangements.

The Wisconsin International Stem Cell Bank, the UK Stem Cell Bank, the Harvard Embryonic Stem Cell collection, and the Massachusetts Stem Cell Bank are prominent examples.  At present, they  allow users of stem cells to obtain them with permission and, typically, a materials agreement from the cell line’s owner (though WiCell owns several of the lines in the Wisconsin International Stem Cell Bank).   They are not involved in negotiations over license terms or eventual commercialization of products.

Examples of registries include: the European Stem Cell Registry, US NIH Registry, the International Stem Cell Registry (University of Massachusetts), International Stem Cell Initiative (ISCI) Stem Cell Registry, UK Stem Cell Bank Registry, Registry of hES Cell Line Provenance (ISSCR – under development), and The Stem Cell Community.  Some registries aim to include intellectual property / data and materials sharing information as part of the registry.

AREAS OF UNCERTAINTY

(1) Defining “Social Benefit.” Although stated norms suggest patenting and proprietary measures be used only when necessary and with attention toward overall social benefit, the content of this norm remains undetermined. Some questions that illustrate this uncertainty include:

• What counts as “social benefit”, and how is it measured and distributed?
• Is hESC science too young to determine how to achieve this balance and determine when a patent is “necessary”?
• Who makes this determination, and how? As most IP policies allow for inventors (or their institutions) to control IP, they are left responsible for this decision.
• How might policies that require revenue sharing (e.g., CIRM) affect patent/license decisions?

(2) Considering Alternative Innovation Regimes. Current norms and policies reflect current regulatory structures – which at present use intellectual property as the main driver of scientific innovation.  Although much depends on how a patent owner chooses to license an invention, historical evidence suggests that patent power tends to lead to restrictive practices.  As such, innovation schemes other than patents remain relatively unexplored.  Alternative innovation schemes include those that operate within current patent regulations (e.g., patent pools or protected commons approaches) or those that supplement it (e.g., prizes or open access). Some pertinent questions include:

• What alternatives exist for encouraging scientific progress in hESC research?
• How can alternatives be explored without threatening hESC research more generally or placing those who attempt alternatives at competitive disadvantage?

(3) Creating Incentives (and Sharing Costs). Incentives to share data (and a fair determination of how to distribute the cost of sharing) and materials remain inadequate.  In spite of general scientific norms about sharing, scientists can be under tremendous personal and institutional pressure not to share.  Data suggest that sharing of materials and data remains inadequate.  In addition, databases similar to the multiple stem cell registries proposed often fold, due to lack of funding.

• What incentives – positive and negative – can be employed, and by whom, to encourage data sharing?
• How can the cost of sharing be fairly distributed?  For example, some stem cell banks report that the cost of sharing a cell line is not fully recouped by current fee arrangements.
• Would better coordination of materials sharing (i.e., cell banks) with data repositories (i.e., registries) better facilitate data and materials sharing (while freeing scientists of the obligation to respond to and fulfill the norm of sharing)?

(4) Developing Accountability and Enforcement Mechanisms. In spite of clear norms to share data promptly and without undue restriction, the content of these norms remain undefined or unenforced.  For example, the NIH requires a data sharing plan, but monitoring is inadequate.  Journals require access to data and materials for other researchers to verify scientific results as a condition of publication, but some apply for more stringent standards.

• Should more attention be given to clear benchmarks for data sharing requirements, similar to CIRM’s 60-day requirement?
• Might funders employ audits of grantee behavior in order to ensure adherence to data and materials sharing policies?
• What are appropriate enforcement mechanisms for non-compliance?  Might stem cell banks or registries become more active in the enforcement of certain norms?

(5) Coordination. Given the diversity of funders, researchers, registries, cell banks, and institutions involved in hESC research, the question of coordination naturally arises.  In many ways – through large institutes and collaborative efforts – hESC research is already more collaborative than typical scientific research. Concerns nevertheless remain. For example, while some call for a single international stem cell registry to avoid duplicative effort, others support the existence of multiple registries in order to see what works best from among these.  More generally, concern exists that “balkanization” of hESC research could result in slower scientific progress; in the US, for instance, some states appear to encourage data and materials sharing within their own jurisdiction rather than between states.  At the same time, efforts spent at coordinating and building a collaborative effort could temporarily slow progress.  Relevant questions include:

• How can coordination be encouraged and facilitated among multiple institutional actors in multiple legal jurisdictions?
• What are the potential costs of coordination, and how can these be minimized?
• If coordination is not equal to harmonization, what policy areas allow for flexibility while maintaining the benefits of a collaborative effort?

CONCLUSION

This briefing document suggests that although superficial agreement generally exists about the norms governing hESC research in the public sector, a significant amount of work remains to clarify, define, and enforce these norms.  Nonetheless, the presence of agreement suggests that progress is possible.  Current limitations include the absence of consideration of private sector norms, and attention only to stated norms (rather than norms as actually practiced, which are more difficult to discover).